Pharmacological profile of survivors of acute myocardial infarction at Turkish academic hospitals

AIM: The purpose of this study was to document treatment profiles in 850 patients surviving acute myocardial infarction at 17 academic hospitals in Turkey. METHODS AND RESULTS: Pharmacological management data of acute myocardial infarction survivors were collected and divided into three categories: drugs which patients received before hospitalization, during the hospitalization, and at hospital discharge. Data regarding medical history, complications during hospitalization, MI extent (Q wave or non-Q wave), infarct location and diagnostic and revascularization procedures were also recorded. This study is based on the 850 patients who met the diagnostic criteria for initial acute MI in the period examined. Among 850 patients with myocardial infarction enrolled 408 (48%) received thrombolytic therapy. The median time interval from symptom onset to initiation of thrombolytic therapy was 196 min. The most commonly used thrombolytic agent was streptokinase (93%). Thrombolytic recipients were younger, and presented sooner after onset of symptoms. Among patients receiving thrombolytic therapy, concomitant pharmacotherapy included aspirin (95%), intravenous heparin (93%), intravenous nitroglycerin (91%), oral beta-blockers (44%), calcium channel antagonists (13%), and angiotensin converting enzyme inhibitors (41%). The lipid lowering therapy was only used in 4% of all patients, and was given to 18% of patients with hyperlipidemia. CONCLUSION: Current usage rates of thrombolytic therapy in Turkey are lower than expected, but when compared with previous reports it increased. Although adjunctive treatment with intravenous heparin and intravenous nitroglycerin is usually used, beta-blockers appear to be underused and calcium channel blockers appear to be overused. The lipid reducing therapies were infrequently prescribed.     

Evaluation of silicosis in ceramic workers

This study is aimed to evaluate the incidence of silicosis and the relation of it with personal and work-related factors among workers exposed to silica in ceramic factory. Workers were evaluated by respiratory symptoms, physical examination, pulmonary function and radiological findings. Occupational and Enviromental Pulmonary Disease Evaluation Questionnaire of the Turkish Thoracic Society Enviromental and Occupational Pulmonary Diseases Working Group was used. 365 of 626 workers had exposure to silica and the rest 261 were concerned as control group. There was no difference between mean age, duration of work and smoking pack year among the groups (p> 0.05). Cough and sputum rates were higher in silicosis group FEV1 and FVC values were lower in silica group but this was not statistically significant. When the two subgroups of silica group (the workers in high dust concentration and the ones in low concentration) were compared, the high concentrated group had significantly more sputum but the other symptoms and pulmonary functional parameters were not different significantly. 24 workers had parenchymal densities adjusted with pneumoconiosis. The workers with the pneumoconistic finding, had a higher mean age and longer duration of work. As a conclusion, ceramic industry has risk for silicosis. And the risk increase by time and age.     

The beneficial effects of 18β-glycyrrhetinic acid following oxidative and neuronal damage in brain tissue caused by global cerebral ischemia/reperfusion in a C57BL/J6 mouse model

This study investigated the effects of 18β-glycyrrhetinic acid (GA) on neuronal damage in brain tissue caused by global cerebral ischemia/reperfusion (I/R) in C57BL/J6 mice. All subjects (n = 40) were equally divided into four groups: (1) sham-operated (SH), (2) I/R, (3) GA, and (4) GA+I/R. The SH group was used as a control. In the I/R group, the bilateral carotid arteries were clipped for 15 min, and the mice were treated with the vehicle for 10 days. In the GA group, mice were given GA (100 mg/kg) for 10 days following a median incision without carotid occlusion. In the GA+I/R group, the I/R model was applied to the mice exactly as in the I/R group, and they were then treated with the same dose of GA for 10 days. Cerebral I/R significantly induced oxidative stress via an increase in lipid peroxidaitons and a decrease in elements of the antioxidant defense systems. However, GA treatment was protective against the oxidative effects of I/R by inducing significant increases in antioxidant defense systems and a significant decrease of lipid peroxidations. Additionally, cerebral I/R increased the incidence of histopathological damage and apoptosis in brain tissue, but these neurodegenerative effects were eliminated by GA treatment. Therefore, the current study demonstrated that GA treatment effectively prevents oxidative and histological damage in the brain caused by global I/R. In this context, GA may be useful for the attenuation of the negative effects of global cerebral I/R and, in the future, it may be a viable and safe alternative treatment for ischemic stroke in humans.     

Hesperidin attenuates oxidative and neuronal damage caused by global cerebral ischemia/reperfusion in a C57BL/J6 mouse model

The aim of this study was to determine the effects of hesperidin (HP) on neuronal damage in brain tissue caused by global cerebral ischemia/reperfusion (I/R) in C57BL/J6 mice. For this purpose, a total of 40 mice were divided equally into four groups: (1) sham-operated (SH), (2) global cerebral I/R, (3) HP, and (4) HP+I/R. The SH group was used as a control. In the I/R group, the bilateral carotid arteries were clipped for 15 min, and the mice were treated with vehicle for 10 days. In the HP group, mice were administered HP (100 mg/kg) for 10 days without carotid occlusion. In the HP+I/R group, the I/R model was applied to the mice exactly as in the I/R group, and they were then treated with 100 mg/kg HP for 10 days. Cerebral I/R significantly induced oxidative stress via an increase in lipid peroxidation and a decrease in the components of the antioxidant defense system. Furthermore, cerebral I/R increased the incidence of histopathological damage and apoptosis in brain tissue. HP treatment significantly reversed the oxidative effects of I/R and inhibited the development of neurodegenerative histopathology. Therefore, the current study demonstrates that HP treatment effectively prevents oxidative and histological damage in the brain caused by global I/R. In this context, the beneficial effects of HP are likely a result of its strong antioxidant and free radical-scavenging properties. HP may be an useful treatment to attenuate the negative effects of global cerebral I/R.     

The impact of diabetes mellitus on peritoneal dialysis: the Turkey Multicenter Clinic Study

Purpose: It is well established that diabetic peritoneal dialysis (PD) patients have a higher mortality rate than the other PD population. This study was designed to determine the overall predictors of survival and compared mortality and morbidity between diabetic and non-diabetic Turkish PD patients. Methods: We conducted a multicenter retrospective study with 915 PD patients [217 had diabetes mellitus (DM)]. Serum albumin, PTH, HbA1c, co-morbid diseases, dialysis adequacy (Kt/V), and peritoneal transport characteristics as well as peritonitis episodes and ultrafiltration failure during the follow-up period were recorded. Results: DM patients were older and had more co-morbidities than non-DM patients. Peritonitis rates were higher in DM patients (one episode per 35.9 patient months) compared to non-DM patients (one episode per 41.5 patient months) (p?p?=?0.022), age (HR 1.03, p?p?p?=?0.038), peripheral artery disease (HR 1.83, p?=?0.025) and amputation (HR 4.1, p?=?0.009) at baseline were significant predictors of overall mortality. Conclusions: Patient survival is lower in diabetic compared to non-diabetic patients on PD. Peritonitis rates were also higher in diabetic PD patients. DM, older age, albumin level and cardiovascular co-morbidities are predictors of mortality     

The suppression of endogenous adrenalin in the prolongation of ketamine anesthesia

This study investigated whether or not the anesthetic effect of ketamine in rats is dependent on adrenal gland hormones. The study was performed on two main rat groups, intact and adrenalectomized. Rat were divided into subgroups and given appropriate doses of ketamine, metyrapone or metyrosine. Durations of anesthesia in the groups were then recorded. Endogenous catecholamine levels were measured in samples taken from peripheral blood. This experimental results showed that ketamine did not induce anesthesia in intact rats at doses of 15 or 30 mg/kg, and that at 60 mg/kg anesthesia was established for only 11 min. However, ketamine induced significant anesthesia even at a dose of 30 mg/kg in animals in which production of endogenous catecholamine (adrenalin, noradrenalin dopamine) was inhibited with metyrosine at a level of 45–47%. Ketamine at 60 mg/kg in animals in which endogenous catecholamine was inhibited at a level of 45–47% established anesthesia for 47.6 min. However, ketamine at 30 and 60 mg/kg induced longer anesthesia in adrenalectomized rats with higher noradrenalin and dopamine levels but suppressed adrenalin production. Adrenalin plays an important role in the control of duration of ketamine anesthesia, while noradrenalin, dopamine and corticosterone have no such function. If endogenous adrenalin is suppressed, ketamine can even provide sufficient anesthesia at a 2-fold lower dose. This makes it possible for ketamine to be used in lengthy surgical procedures.     

The neutralization effect of montelukast on SARS-CoV-2 is shown by multiscale in silico simulations and combined in vitro studies

Small molecule inhibitors have previously been investigated in different studies as possible therapeutics in the treatment of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In the current drug repurposing study, we identified the leukotriene (D4) receptor antagonist montelukast as a novel agent that simultaneously targets two important drug targets of SARS-CoV-2. We initially demonstrated the dual inhibition profile of montelukast through multiscale molecular modeling studies. Next, we characterized its effect on both targets by different in vitro experiments including the enzyme (main protease) inhibition-based assay, surface plasmon resonance (SPR) spectroscopy, pseudovirus neutralization on HEK293T/hACE2+TMPRSS2, and virus neutralization assay using xCELLigence MP real-time cell analyzer. Our integrated in silico and in vitro results confirmed the dual potential effect of montelukast both on the main protease enzyme inhibition and virus entry into the host cell (spike/ACE2). The virus neutralization assay results showed that SARS-CoV-2 virus activity was delayed with montelukast for 20 h on the infected cells. The rapid use of new small molecules in the pandemic is very important today. Montelukast, whose pharmacokinetic and pharmacodynamic properties are very well characterized and has been widely used in the treatment of asthma since 1998, should urgently be completed in clinical phase studies and, if its effect is proved in clinical phase studies, it should be used against coronavirus disease 2019 (COVID-19).